The field of this invention relates to miniaturized flow systems, and in particular, to a microfluidics device composed of two or more layers or laminae, each containing a microfluidics structure.
Microfluidic devices permit numerous operations with small volumes. Devices available today have two-dimensional flow systems, where all of the channels and microstructures are in the same plane. The microfluidic devices lend themselves to the movement of solutes and fluids by means of electric fields and pneumatics. The microfluidic devices allow for accurate control of dispensing volumes from one channel to the next. These structures have proven very versatile in performing numerous operations that had previously been performed on a macro scale. For example, DNA sequencing, high-throughput drug screening, chemistries, such as organic synthesis and diagnostics, have all found application.
While for many applications having a planar system is adequate, greater versatility of the microfluidic systems may be achieved with flow systems in three dimensions. By having channels and reservoirs in different planes, where the channels and/or reservoirs are interconnected, the number of solutions or solutes that can be mixed or fed to a receptacle, as well as the timing of such operations, is greatly expanded. Such a three-dimensional flow pattern would also permit a greater number of operations within a single microfluidic device having a small footprint.
The present-day devices are frequently prepared using molding techniques. By preparing a negative mold that can impress microstructures, such as trenches or channels and reservoirs, in a solid substrate, a flow pattern can be formed for performing various operations. The trenches and channels are operated enclosed, so a cover is bonded to the surface of the substrate, where openings for the reservoirs may have been formed in the substrate or are provided in the cover. The trenches or channels are usually quite small, having cross-sectional areas in the range of about 5 to 50,000 xcexcm2, frequently less than 10,000 xcexcm2. In carrying out the operations it is generally necessary that there be highly concentrated solute plugs that are manipulated. Variations in the shape or cross-section of the channels results in distortions in the plug and can affect the movement in the channel. When applying the cover, it is essential that there be little, if any, change in the shape of the channels, that the connections between channels be substantially unaffected and that the surface of the channels be unchanged. This requires great care in the manner of sealing and the materials used for sealing. The problems of sealing become exacerbated when dealing with multiple layers of fluid networks, where the channels in different planes connect to permit fluid flow from one plane to the next.
Also, there continues to be a demand for performing more assays or sample determinations in shorter periods of time. Microfluidic device technology has already demonstrated improvements over traditional bench-top methods such as faster electrophoretic separations and higher sample throughputs. Nonetheless, new structures or designs that improve the current level of operation of microfluidic devices are desired. Further, providing high-density devices in a smaller footprint permits a reduction in the size of fluid handling and detection devices that would interface with such devices.
U.S. Pat. No. 5,904,424 describes a device for mixing small quantities of liquids. WO 99/56862 describes a micromachined mixer for microfluidic analytical systems.
The invention includes, in one aspect, a microfluidics device composed of first and second laminae, each having confronting inner surfaces at which the two laminae are bonded together, and opposite outer surfaces. A first channel microstructure includes a channel formed in the first lamina adjacent the first-lamina inner surface, and one or more reservoirs in fluid communication with the first-lamina channel. A second channel microstructure includes a channel formed in the second lamina adjacent the second-lamina inner surface. The first-lamina and second-lamina channels are enclosed by non-channel regions of the inner surfaces of the second and first laminae, respectively, and are in communication through one or more vias formed where a region of the first-lamina channel overlaps a region of the second-lamina channel. One or more openings formed in one or both laminae provide communication between the outer surface(s) of the lamina(e) and one or more reservoirs in the device. Liquid components contained in the first-lamina channel microstructure may be directed into the second-lamina channel microstructure through the via(s).
The second-lamina channel microstructure may also include one or more reservoirs communicating with the second-lamina channel. The one or more openings may communicate with the outer surface of at least one surface with reservoirs in both the first-lamina and second-lamina channel microstructures. The one or more reservoirs are adapted to receive an electrode in contact with liquid contained in the reservoirs, such that application of a voltage potential across selected electrodes is effective to move an electrolyte solution or charged components in a solution within the channel microstructures in each lamina and between the first-lamina and second-lamina microstructures.
In one embodiment, the first-lamina microstructure includes a sample-holding well and a sample channel in communication therewith, the second-lamina includes intersecting side and separation channels, and a sample-loading region in the separation channel where the two channels intersect. The sample channel in the first lamina has a region of overlap with the side channel in the second lamina, such that solution or solution components in the sample well can be moved into the sample-loading region through the via, and separation of charged sample components in the sample-loading zone can be achieved by applying a potential difference across reservoirs communicating with opposite ends of the separation channel.
In another embodiment, the first-lamina microstructure includes a first separation channel communicating at opposite ends thereof with first-separation channel reservoirs, the second-lamina microstructure includes a second separation channel communicating at opposite ends thereof with second-separation channel reservoirs, and (iii) the first and second separation channels communicate through a via which allows sample material separated by movement along the first separation channel to be loaded into the second separation channel, for further separation therein.
In particular, the second-lamina microstructure may includes a plurality of second separation channels, each communicating with one of a plurality of vias that communicate with the first separation channel at spaced intervals along the length thereof, allowing a plurality of sample components separated in the first separation channel to be further separated by movement along each of the plurality of second separation channels.
In still another embodiment, the first-lamina microstructure includes a first separation channel communicating at opposite ends thereof with first-separation channel reservoirs, and the second-lamina microstructure includes a plurality of sample-processing stations at which sample-processing steps can occur. Each station communicates with one of a plurality of vias that communicate with the first separation channel at spaced intervals along the length thereof, allowing a plurality of sample components separated in the first separation channel to be further processed by movement into a selected processing station.
These and other objects and features of the invention will become more fully apparent when the following detailed description of the invention is read in conjunction with the accompanying drawings.